The spiking and secretory activity of oxytocin neurones in response to osmotic stimulation: a computational model

J Physiol. 2019 Jul;597(14):3657-3671. doi: 10.1113/JP278045. Epub 2019 Jun 9.

Abstract

Key points: A quantitative model of oxytocin neurones that combines a spiking model, a model of stimulus-secretion coupling and a model of plasma clearance of oxytocin was tested. To test the model, a variety of sources of published data were used that relate either the electrical activity of oxytocin cells or the secretion of oxytocin to experimentally induced changes in plasma osmotic pressure. To use these data to test the model, the experimental challenges involved were computationally simulated. The model predictions closely matched the reported outcomes of the different experiments.

Abstract: Magnocellular vasopressin and oxytocin neurones in the rat hypothalamus project to the posterior pituitary, where they secrete their products into the bloodstream. In rodents, both vasopressin and oxytocin magnocellular neurones are osmoresponsive, and their increased spiking activity is mainly a consequence of an increased synaptic input from osmoresponsive neurons in regions adjacent to the anterior wall of the third ventricle. Osmotically stimulated vasopressin secretion promotes antidiuresis while oxytocin secretion promotes natriuresis. In this work we tested a previously published computational model of the spiking and secretion activity of oxytocin cells against published evidence of changes in spiking activity and plasma oxytocin concentration in response to different osmotic challenges. We show that integrating this oxytocin model with a simple model of the osmoresponsive inputs to oxytocin cells achieves a strikingly close match to diverse sources of data. Comparing model predictions with published data using bicuculline to block inhibitory GABA inputs supports the conclusion that inhibitory inputs and excitatory inputs are co-activated by osmotic stimuli. Finally, we studied how the gain of osmotically stimulated oxytocin release changes in the presence of a hypovolaemic stimulus, showing that this is best explained by an inhibition of an osmotically regulated inhibitory drive to the magnocellular neurones.

Keywords: hypothalamus; hypovolemia; lamina terminalis; osmotic pressure; posterior pituitary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Bicuculline / pharmacology
  • Computer Simulation
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Osmosis / drug effects
  • Osmosis / physiology*
  • Osmotic Pressure / drug effects
  • Osmotic Pressure / physiology
  • Oxytocin / metabolism*
  • Rats
  • Supraoptic Nucleus / drug effects
  • Supraoptic Nucleus / metabolism
  • Vasopressins / drug effects
  • Vasopressins / metabolism

Substances

  • Vasopressins
  • Oxytocin
  • Bicuculline